# Metabolic crosstalk through vascular endothelium-secreted factors

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $467,406

## Abstract

Endothelial cells interface blood and tissues for nutrient and fluid transport between organs.
Therefore, endothelial cells critically provide fatty acids and other carbon fuels to meet tissue
demands during periods of nutrient limitation. Despite vital interorgan communication roles for
endothelial cells, we lack fundamental insight into how endothelial cells serve systemic
metabolism and the responses to food and environmental challenges.
Metabolic disorders such as obesity and insulin resistance reflect the combined impacts of genetic
and environmental factors that alter the ways the liver and adipose tissues govern energy balance.
Therefore, precise strategies must activate or repress metabolic pathways in the liver and adipose
tissues to maintain the energetic needs of connected organ systems. In the previous funding cycle,
we established that circulating bone morphogenetic protein-binding endothelial regulator (BMPER)
promoted hepatic insulin sensitivity in multiple mouse models of diabetes. In addition, human
BMPER gene variants and its protein plasma level were strongly associated with obese
parameters. The subsequent experiments demonstrated BMPER abundance in blood coincides
with nutrient availability. Fasting in rodents and people increased BMPER levels in blood while
feeding caused a coincident reduction in bioavailable BMPER. Mechanistically, our preliminary
data suggest fasting causes BMPER release from the liver, which acts on adipose tissue to
liberate free fatty acids and glycerol for gluconeogenesis. Peroxisome proliferator activated
receptor alpha activation heightens BMPER expression in the liver upon fasting. However, this
signaling axis is likely dysregulated by high fat-diet feeding. Based on our preliminary data, we
hypothesize that fasting-induced BMPER in the liver acts as an endocrine stimulator of lipolysis
in adipose tissue. We will test our hypothesis by defining how BMPER influences fatty acid
mobilization in adipose tissue; establishing mechanisms governing BMPER regulation of
adipocyte lipolysis; and determining nutrient sensing transcription factors that regulate BMPER
availability in serum. Our studies will define a new liver-to-adipose tissue circuit mediated by
BMPER in the regulation of energy homeostasis and offer new insight into whether BMPER
signaling can be leveraged for the treatment of obesity, diabetes and other metabolic disorders.

## Key facts

- **NIH application ID:** 10879459
- **Project number:** 2R01DK123186-04A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Xinchun Pi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $467,406
- **Award type:** 2
- **Project period:** 2020-09-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879459

## Citation

> US National Institutes of Health, RePORTER application 10879459, Metabolic crosstalk through vascular endothelium-secreted factors (2R01DK123186-04A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10879459. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*